Despite the enormous variety of cancers which are described in details in the medical literature, such as cancer of the lung, colon, rectum, prostate, breast, brain, liver and intestine, all type of cancers are characterized primarily by an increase in the number of abnormal cells derived from a given normal tissue, invasion of adjacent tissues by these abnormal cells, or lymphatic or blood-borne spread of malignant cells to regional lymph nodes and to distant sites (metastasis).
Malignant transformation of normal cells is a complex process featuring frequent genetic and epigenetic alterations that lead to the activation of oncogenes and inactivation of tumor suppressor genes (Kodama et al., In Vivo. 2000 November-December; 14(6):725-34). Contrary to healthy cells that control their own growth and will goes into apoptosis if they become unhealthy, neoplastic cells escape this protective system and grow uncontrollably.
HIP/PAP has been shown to combine mitogenic and antiapoptotic functions through the PKA signalling pathway. In particular HIP/PAP has been demonstrated to promote liver regeneration and may therefore be particularly useful in case of liver resection in order to improve liver function and suppress or limit liver failure. Indeed, using an in vivo model of liver failure (e.g.: HIP/PAP and c-myc bi-transgenic mice, in which c-myc is specifically expressed in the liver using woodchuck hepatitis regulatory sequences), it has been shown that overexpression of HIP/PAP improved mice survival, (U.S. patent application Ser. No. 13/032,521 and WO 2004/112824, Simon et al, FASEB J. 2003 August; 17(11):1441-50).
While the expression of HIP/PAP has been shown to be negatively correlated with the depth of invasions of CRC (Colorectal carcinoma), no significant relationship has been found between expression of PAP protein and the clinical outcome of patients, Duke's state of tumors, or tumor localization, size or differentiation degree (Zheng et al., J Histochem Cytochem. 2011 January; 59(1):106-15; Rechreche et al., Int J Cancer. 1999 May 31; 81(5):688-94). Furthermore, HIP/PAP is highly expressed during human primary liver cancer and is a member of the Reg family that has been suggested to function as tissue mitogens (Dieckgraefe et al., U.S. Pat. No. 7,510,708).
The incidence of cancer continues to climb as the general population ages, as new cancers develop, and as susceptible populations (e.g., people infected with AIDS or excessively exposed to sunlight) grow. A tremendous demand therefore exists for new method and compositions that can be used to treat patients with cancer.
Current cancer therapies may involve surgery, chemotherapy, hormonal therapy and/or radiation treatment to eradicate neoplastic cells in a patient (see, for example, Stocldale, 1998, Medicine, vol. 3, Rubenstein and Federman, eds., Chapter 12, Section IV). Recently, cancer therapy could also involve biological therapy or immunotherapy. All of the approaches pose significant drawbacks for the patient. Surgery for example, may be contraindicated due to the health of a patient. Additionally, surgery may not completely remove neoplastic tissue. Further, radiation therapy as well as chemotherapy, hormonal therapy and biological therapy elicit numerous and serious side effects.
Therefore, there is still a significant need for alternative safe and effective composition for use in treating and/or managing cancer, while reducing or avoiding the toxicities and/or side effects associated with the conventional treatments.